ArticleThe international journal of neuropsychopharmacology2014
Amphetamine decreases α2C-adrenoceptor binding of [11C]ORM-13070: a PET study in the primate brain.
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11 citing papers in PubMed, 16 citations in OpenAlex.
- Sensitivity of [(11)C]ORM-13070 to increased extracellular noradrenaline in the CNS - a PET study in human subjects.Psychopharmacology · 2015Trial
- PET Radiotracers for CNS-Adrenergic Receptors: Developments and Perspectives.Molecules (Basel, Switzerland) · 2020Review
- Amphetamine improves rat 5-choice continuous performance test (5C-CPT) irrespective of concurrent low-dose haloperidol treatment.Psychopharmacology · 2020Article
- Quantitative Rodent Brain Receptor Imaging.Molecular imaging and biology · 2020Review
- Effects of Exercise on Cognitive Performance in Children and Adolescents with ADHD: Potential Mechanisms and Evidence-based Recommendations.Journal of clinical medicine · 2019Review
- Hunting for the high-affinity state of G-protein-coupled receptors with agonist tracers: Theoretical and practical considerations for positron emission tomography imaging.Medicinal research reviews · 2019Review
- Serotonin concentration enhancers at clinically relevant doses reduce [Translational psychiatry · 2018Article
- The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities.Neuroscience and biobehavioral reviews · 2018Review
- Potential Effect of Prolonged Sevoflurane Anesthesia on the Kinetics of [Molecular imaging and biology · 2018Article
- Therapeutic Potential of Selectively Targeting the αFrontiers in psychiatry · 2017Review
- Application of cross-species PET imaging to assess neurotransmitter release in brain.Psychopharmacology · 2015Review
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Authors and funding
18 authors at 6 institutions in 3 countries.
Sjoerd J FinnemaKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde) sjoerd.finnema@ki.se.
Zoë A HughesKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Merja Haaparanta-SolinKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Vladimir StepanovKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Ryuji NakaoKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Katarina VarnäsKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Andrea VarroneKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Eveliina ArponenKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Päivi MarjamäkiKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Katariina PohjanoksaKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Lauri VuorilehtoKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Phebian A BabalolaKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Olof SolinKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Sarah GrimwoodKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Jukka SallinenKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Lars FardeKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Mika ScheininKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Christer HalldinKarolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden (Drs Finnema, Stepanov, Nakao, Varnäs, Varrone, Farde, and Halldin); Pfizer, Neuroscience Research Unit, Cambridge, MA (Drs Hughes, Babalola, and Grimwood); University of Turku, Turku PET Centre, Turku, Finland (Drs Haaparanta-Solin, Arponen, Marjamäki, and Solin); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, and Turku University Hospital, Unit of Clinical Pharmacology, Turku, Finland (Drs Pohjanoksa, Vuorilehto, and Scheinin); Orion Corporation, Orion Pharma, Research and Development, Turku, Finland (Dr Sallinen); AstraZeneca, Translational Science Center at Karolinska Institutet, Stockholm, Sweden (Dr Farde).
Turku University Hospital · FIKarolinska Institutet · SEPfizer (United States) · USAstraZeneca (Sweden) · SETurku PET Centre · FIOrion Corporation (Finland) · FI
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe neurotransmitter norepinephrine has been implicated in psychiatric and neurodegenerative disorders. Examination of synaptic norepinephrine concentrations in the living brain may be possible with positron emission tomography (PET), but has been hampered by the lack of suitable radioligands.
methodsWe explored the use of the novel α2C-adrenoceptor antagonist PET tracer [(11)C]ORM-13070 for measurement of amphetamine-induced changes in synaptic norepinephrine. The effect of amphetamine on [(11)C]ORM-13070 binding was evaluated ex vivo in rat brain sections and in vivo with PET imaging in monkeys.
resultsMicrodialysis experiments confirmed amphetamine-induced elevations in rat striatal norepinephrine and dopamine concentrations. Regional [(11)C]ORM-13070 receptor binding was high in the striatum and low in the cerebellum. After injection of [(11)C]ORM-13070 in rats, mean striatal specific binding ratios, determined using cerebellum as a reference region, were 1.4±0.3 after vehicle pretreatment and 1.2±0.2 after amphetamine administration (0.3mg/kg, subcutaneous). Injection of [(11)C]ORM-13070 in non-human primates resulted in mean striatal binding potential (BP ND) estimates of 0.65±0.12 at baseline. Intravenous administration of amphetamine (0.5 and 1.0mg/kg, i.v.) reduced BP ND values by 31-50%. Amphetamine (0.3mg/kg, subcutaneous) increased extracellular norepinephrine (by 400%) and dopamine (by 270%) in rat striata.
conclusionsTogether, these results indicate that [(11)C]ORM-13070 may be a useful tool for evaluation of synaptic norepinephrine concentrations in vivo. Future studies are required to further understand a potential contribution of dopamine to the amphetamine-induced effect.
Indexed as
Positron-Emission TomographyAdrenergic alpha-2 Receptor AntagonistsAdrenergic Uptake InhibitorsAmphetamineAnimalsAtomoxetine HydrochlorideBrainCentral Nervous System StimulantsDioxanesFemaleHumansImidazolesMacaca fascicularisMalePiperazinesPropylamines1-(1-(2,3-dihydrobenzo(1,4)dioxin-2-yl)methyl)-4-(3-methoxymethylpyridin-2-yl)piperazineAdrenergic alpha-2 Receptor AntagonistsAdrenergic Uptake InhibitorsAmphetamineatipamezoleAtomoxetine HydrochlorideCentral Nervous System StimulantsDioxanesImidazolesPiperazinesPropylaminesRadiopharmaceuticalsReceptors, Adrenergic, alpha-2amphetamineatipamezoleatomoxetinemonkeyPET
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